A Myocardial Infarction (MI) or heart attack, occurs when the blood supply to some part of the heart muscle (myocardium) is abruptly stopped. This is often due to clotting in a coronary blood vessel. Blood supplying the heart muscle comes entirely from two coronary arteries, both lying along the outside surface of the heart. If one of these arteries or any part of one suddenly becomes blocked, the area of the heart being supplied by the artery dies. The death of a portion of the heart muscle is a myocardial infarct, and the amount of the heart affected by the sudden occlusion will determine the severity of the attack. If the heart continues to function, the dead portion is eventually walled off as new vascular tissue supplies the needed blood to adjacent areas.
According to the American Heart Association, in the year 2000 approximately 1,100,000 new myocardial infarctions occurred in the United States. For 650,000 patients this was their first myocardial infarction, while for the other 450,000 patients this was a recurrent event. Two hundred-twenty thousand people suffering MI die before reaching the hospital. Within one year of the myocardial infarction, 25% of men and 38% of women die. Within 6 years, 22% of Men and 46% of women develop chronic heart failure, of which 67% are disabled.
An MI starts when a coronary artery suddenly becomes occluded and can no longer supply blood to the myocardial tissue. When a myocardial infarction occurs, the myocardial tissue that is no longer receiving adequate blood flow dies and is replaced with scar tissue. Within seconds of a myocardial infarction, the under-perfused myocardial cells no longer contract, leading to abnormal ventricular wall motion, high wall stresses within and surrounding the infarct, and depressed ventricular function. The infarct expansion and ventricular remodeling are caused by these high stresses at the junction between the infracted (not contracting) tissue and the normal myocardium. These high stresses eventually kill or severely depress function in the still viable myocardial cells. This results in a wave of dysfunctional tissue spreading out from the original myocardial infarct region.
Left ventricular remodeling is defined as changes in shape and size of the Left Ventricle (LV) that can follow a MI. The process of LV enlargement can be influenced by three independent factors that is, infarct size, infarct healing and LV wall stress. The process is a continuum, beginning in the acute period and continuing through and beyond the late convalescent period. During the early period after MI the infarcted region is particularly vulnerable to distorting forces. This period of remodeling is called infarct expansion. The infarct expansion phase of remodeling starts on the first day of MI (likely several hours after the beginning of the MI) and lasts up to 14 days. Once healed, the infarcted tissue or “scar” itself is relatively non distensible and much more resistant to further deformation. Therefore late enlargement is due to complex alterations in LV architecture involving both infarcted and non-infarcted zones. This late chamber enlargement is associated with lengthening of the contractile regions rather than progressive infarct expansion. Post infarction LV aneurysm (a bulging out of the thin weak ventricular wall) represents an extreme example of adverse remodeling that leads to progressive deterioration of function with symptoms and signs of congestive heart failure.
Effective treatments for MI are acute and can be only implemented immediately after the occlusion of the coronary vessel. The newest approaches include aggressive efforts to restore patency to occluded vessels broadly called reperfusion therapies. This is accomplished through thrombolytic therapy (with drugs that dissolve the thrombus) or increasingly with primary angioplasty and stents. Reopening the occluded artery within hours of the initial occlusion can decrease tissue death, and thereby decrease the total magnitude of infarct expansion, extension, and ventricular remodeling. These treatments are effective but clearly not satisfactory alone. In many cases, patients arrive at the appropriately equipped hospital too late for these acute therapies. In other cases, their best efforts fail to reopen blood vessels sufficiently to arrest expansion of the infarct. These therapies are also associated with considerable risk to the patient and high cost.
Chronic post-infarct treatments include pharmaceuticals such as ACE inhibitors, beta blockers, diuretics, and Ca channel antagonists. These agents have multiple effects, but share in the ability to reduce aortic pressure, and thereby cause a slight decrease in wall stress. These agents have been shown to slow the ventricular remodeling process. Nevertheless, their ability to reduce the infarct expansion is limited by side effects such as hypotension (pathologically low blood pressure) that can be fatal to a patient.
Experimental surgical treatments include approaches to exclude, isolate, or remove the infarct region (such as the Dor procedure). The Dor procedure, also called Endoventricular Patch Plasty, consists in suturing a patch inside the ventricle within the limits of the fibrous scar. Other potential surgical approaches include the application of heat to shrink the infarcted tissue, followed by the suturing of a patch onto the infarcted region.
Other treatments envision surrounding the heart, or a significant portion thereof, with a jacket. Kelley et al (“Restraining infarct expansion preserves LV geometry and function after acute anteroapical infarction,” Circulation. 1999; 99: 135-142) tested the hypothesis that restraining expansion of an acute infarction preserves LV geometry and resting function. Pilla et al (“Ventricular Constraint Using the Acorn Cardiac Support Device (CSD) Limits Infarct Expansion in an Ovine Model of Acute Myocardial infarction,” Journal of Cardiac Failure 2001; 7 Suppl. 2: 40) described that constraining the whole heart with a surgically placed cup limited the infarct expansion in animals. An experimental CSD device used to restrain the heart in the Pilla study was made by the Acorn Cardiovascular Inc. of St. Paul, Minn. The Acorn device, a textile girdle or so-called “cardiac wrap,” is wrapped around both the left and right ventricles, thereby preventing further enlargement of the heart. Description of the Acorn device can be found in the U.S. Pat. No. 5,702,343 “Cardiac reinforcement device” and many patents that derived from it. The CSD device has very limited practical value for the treatment of infarct expansion since it requires major open-heart surgery to install. Once installed, the CSD cannot be removed without exposing the patient to additional risks.
Many more scientific studies show that constraining the heart in the hours and days following the acute MI can reduce the extent of damage to the heart. Benefits exhibited by constraining the heart during and after the infarct expansion can be traced down to the relationship between the changing geometry of the heart and the stress in the heart muscle that forms the ventricular wall. The Law of LaPlace says that wall tension is proportional to the product of intraventricular pressure and ventricular radius.
Wall tension can be thought of as the tension generated by the heart muscle fibers that results in a given intraventricular pressure at a particular ventricular radius. Therefore, when the ventricle needs to generate greater pressure, for example with the increased afterload (aortic pressure) the wall tension is increased. This relationship also shows us that a dilated ventricle (as occurs after an MI or in dilated cardiomyopathy) has to generate increased wall tension to produce the same intraventricular pressure.
Left Ventricle (LV) enlargement must occur after a large infarct in order to maintain or restore cardiac output in the presence of the loss of the significant amount of contracting muscle tissue. The LV enlargement is necessary to compensate for this loss. In fact, an enlarged ventricle can eject a larger stroke volume, despite unchanged fiber shortening. The disadvantage of dilatation is the extra workload imposed on normal, residual myocardium and the increase in wall tension (according to the LaPlace Law), which represent the stimulus for hypertrophy. If hypertrophy is not adequate to match increased tension, then a vicious cycle will start which determines further and progressive dilatation. The described mechanism explains how an infarct that at the end of the expansion process exceeds certain size is likely to trigger the long-term irreversible sequence of hypertrophy, dilation and chronic heart failure leading to disability and death.
In addition to the Acorn CSD device, various existing designs of heart constraining mechanisms are described in detail in the following U.S. Patents:                U.S. Pat. No. 5,702,343 Cardiac reinforcement device        U.S. Pat. No. 6,077,218 Cardiac reinforcement device        U.S. Pat. No. 6,085,754 Cardiac disease treatment method        U.S. Pat. No. 6,123,662 Cardiac disease treatment and device        U.S. Pat. No. 6,126,590 Cardiac reinforcement device        U.S. Pat. No. 6,155,972 Cardiac constraint jacket construction        U.S. Pat. No. 6,165,121 Cardiac reinforcement device        U.S. Pat. No. 6,165,122 Cardiac reinforcement device        U.S. Pat. No. 6,174,279 Cardiac constraint with tension indicator        U.S. Pat. No. 6,193,648 Cardiac constraint with draw string tensioning        U.S. Pat. No. 6,241,654 Cardiac reinforcement devices and methods        U.S. Pat. No. 6,293,906 Delivery of cardiac constraint jacket        U.S. Pat. No. 6,332,863 Heart wall tension reduction kit        U.S. Pat. No. 6,332,864 Heart wall tension reduction apparatus        U.S. Pat. No. 6,375,608 Cardiac reinforcement device        U.S. Pat. No. 6,402,679 External stress reduction device and method        U.S. Pat. No. 6,402,680 Stress reduction apparatus and method        U.S. Pat. No. 6,416,459 Bag for at least partially enveloping a heart        U.S. Pat. No. 6,425,856 Cardiac disease treatment and device        U.S. Pat. No. 6,482,146 Cardiac disease treatment and device        U.S. Pat. No. 6,494,825 System for stress relieving the heart muscle and for controlling heart function.        
In spite of the great diversity of shapes, materials and forms, all of these constraint methods and mechanisms are not suited to fulfill the objectives of this invention. The prior cardiac constraints are described as socks, girdles, cups, wraps, bands, belts, bladders and pockets that are surgically placed around the heart, or outside of the pericardium, to prevent it from expanding beyond certain desired size. These devices are intended for chronic treatment to produce benefit over the years in the late stages of ventricular remodeling, long after the infarct expansion stage. All of the prior art devices require major surgery to install. Once installed, they cannot be “turned off” or removed easily.
U.S. Pat. No. 6,463,332 “Method and system for pericardial enhancement” describes a unique method of constraining the heart by changing the properties of the human pericardium. Pericardium is a sac-like membrane that contains the heart. The invention modifies the pericardium to treat patients suffering from or at risk of heart failure to prevent remodeling of the heart. Methods and apparatus are provided for stiffening, strengthening, tightening, reshaping, and/or shrinking the pericardium to enhance the restraining and supporting capability of the pericardium around the heart.
In spite of the great diversity of the described methods of constraining the heart and their proven benefit of the reduction of the infarct expansion there is no demonstrated commercial success or even clinical benefit. The limitations of the known heart constraints are the difficulty and risks of the surgical implantation technique, lack of adjustability and the irreversibility of the implant.
Despite spectacular improvements in MI therapy, within one year of the myocardial infarction, 25% of men and 38% of women die. The total number and incidence of heart failure continues to rise with over 500,000 new cases each year. Approximately 85% of these new cases of heart failure are a direct consequence of a large MI. While considerable progress has been made in acute reperfusion of the heart immediately after the MI, heart remodeling and infarct expansion that follows is not treated effectively. There is a clear clinical need for a novel treatment that can be applied shortly after the MI to reduce the extent of the infarct expansion.